A-hydroxylation of ketones

The hydroxyl group in alcohol 122 is then oxidized. Deprotonation of this ketone with KHMDS (1 eq.), followed by the addition of Davis oxaziridine (see Chapter 4 for a-hydroxylation of ketones)28 (2 eq.) allows the stereo-controlled introduction of the C-10 oxygen from the less hindered enolate face, providing only the (i )-hydroxyketone 123. Subsequent reduction of 123 with excess LAH provides the tetra-ol 124. Treatment of this compound with imidazole and TBSC1 followed by PPTS and 2-methoxypropene provides in one operation the acetonide 125 with 91% yield (Scheme 7-37). 

Asymmetric a-hydroxylation of ketones 97 through phase transfer catalysis under alkaline conditions was realized by use of the Merck catalyst 7 (R=4-CF3, X=Br)[721 as well as the chiral azacrown ether 98[731 in conjunction with molecular oxygen, as shown in Scheme 30. The highest enantioselectivity of 79% ee was attained in the a-hydroxylation of the tetralone 100 by use of the Merck cata-... 

The procedure reported here provides a convenient method for the a-hydroxylation of ketones which form enolates under the reaction conditions. The reaction has been applied successfully to a series of para-substituted acetophenones, 1-phenyl-1-propanone, 3-pentanone, cyclopentanone, cyclohexanone, cycloheptanone, cyclododecanone, 2-methyl cyclohexanone, 2-norbornanone and benzalacetone. In the case of a steroidal example it was shown that a carbon-carbon double bond and a secondary hydroxyl group are not oxidized. A primary amino function, as in the case of p-aminoacetophenone, is not affected.5 Similarly, a tertiary amino ketone such as tropinone undergoes the a-hydroxy at ion reaction.5... 

Ketones can be a hydroxylated in good yields, without conversion to the enolates, by treatment with the hypervalent iodine reagents162 o-iodosobenzoic acid163 or phenyliodoso acetate PhI(OAc)2 in methanolic NaOH.164 The latter reagent has also been used on carboxylic esters.165 02 and a chiral phase transfer catalyst gave enantioselective a hydroxylation of ketones, if the a position was tertiary.166... 

A catalytic route using a manganese (III) complex has been developed for a-hydroxylation of ketones avoiding the use of water or a protic solvent mixtures of a-hydroxyketones and their silyl derivatives were formed in excellent yield. By using a chiral pyrrolidine-based manganese (III) complex as catalyst, asymmetric oxidation was effected, with enantiomeric excess varying from 14 to 62% [30], Another kind of a-functionalized ketones resulted from silyl enol ethers which after the addition of IOB.BF3 were treated with triethyl phosphite a-ketophosphonates were obtained in this way [31] ... 

HYDROXY-1-CYCLOHEXENE-1-CARBOXALDEHYDE 1-CYCLOHEXENE-1 -CARBOXALDEHYDE, 3-HYDROXY- (67252-14-6), 67, 205 (S)-(+)-3-HYDROXY-2,2-DIMETHYLCYCLOHEXANONE Cyclohexanone, 3-hydroxy-2,2-dimethyl-, (S)- (87655-21-8), 68, 56 Hydroxylamine, N-phenyl-, 67, 187 a-Hydroxylation of ketones, 66, 138... 

One of the oldest methods for effecting the a-hydroxylation of ketones utilizes transition metal salts, the most widely employed being lead tetraacetate (LTA). Treatment of enolizable ketones with LTA (usually at reflux in acetic acid or benzene) affords the corresponding a-acetoxy derivatives. Originally a radical mechanism was proposed (Scheme 1), but elsewhere it has been suggested that an incipient or-ganolead species is involved prior to conversion to the a-acetoxy derivative by inter- or intra-molecular nucleophilic attack (Scheme 2). 

Much of the preceding discussion concerning the a-hydroxylation of ketones is relevant for ester and lactone substrates. Many examples have featured B-keto esters and these are clearly relevant. Reference should be made to these sections. 

The procedure developed by Moriarty for the a-hydroxylation of ketones using iodosylbenzene or its diacetate has been extended fw use with esters.Thus treatment of methyl or ethyl esters with iodosylbenzene diacetate in a two-phase system (benzene/aqueous KOH) generates the a-hydroxy acid, while reaction in methanol in the presence of sodium methoxide provides the a-methoxy ester, (Scheme 19). Oxidation of the fnt acid was unsuccessful (Section 2.3.2.6). Both variations proceed in similar, moderately good yields, in a fashion mechanistically analogous to Ae reaction with ketones. 

Recent introduction of these reagents as a source of electrophilic oxygen for a variety of oxidative processes was extended to the a-hydroxylation of ketone enolates (Section 2.4.2.1.Ziii), and, at the same time, to the analogous ester/lactone oxidations. 

In a maimer exactly analogous to the a-hydroxylation of ketone silyl enol ethers (Sections 2.3.2.1.3.i and 2.3.2.2.3.i) the corresponding ester silyl ketene acetals may be epoxidized by poacid and subsequently cleaved with fluoride to reveal the a-hydroxy ester.Yiel are good if hexanes are employed as solvent, while competing hydrolysis hampers the process in other media. The equivalent lactone hydroxylations are, however, not possible since hydrolysis is the dominant process even in hexane. This solvent limitation may prove restrictive to the widespread use of this technique. 

In a paper emphasizing the preparative value, Schulz and Kluge described the a-hydroxylation of ketones in good yields by using 2 equivalents of triarylarainium salts in moist acetonitrile [172]. In contrast to the oxidative functionalization of 68, 70 and 72 the reaction with cyclohexanone (64) and methyl isopropyl ketone (80) was run in the presence of a hindered pyridine base. Thus, mechanistically, it cannot rigorously be stated whether ends or the enolates are oxidized (cf Sect. 3.2). 

Hydrogen peroxide in the presence of catalytic amounts of methyltrioxorhenium(VII), ReMeOs, is a convenient and efficient method for the a-hydroxylation of ketones. Particularly interesting is the HiOi/cetylpyridinium peroxotungstophosphate system which, under phase transfer conditions, provides a facile method for preparing aldehydes with one carbon atom less than the parent precursors. The ratio of the products changes with the experimental conditions. 

The organocatalytic asymmetric a-hydroxylation of ketones with A -sulfonyloxaziridines was studied by Engqvist et al. <2005TL2053>. For example, the direct diamine-catalyzed enantioselective a-hydroxylation of ketones 255 with 7ra S -2-/>-tolylsulfonyl-3-phenyloxaziridine 33 in the presence of chiral diamine 256 afforded the corresponding a-hydroxylated products 257 in moderate yields with up to 63% ee. 

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